Depolarization-induced Ca2+ Release

DICR (depolarization-induced Ca2+ release) is Ca2+ release triggered by depolarization of the sarcolemma. In skeletal muscle, conformational change in the voltage sensor (a 1S subunit of the dihydropyridine receptor) in the T-tubule is directly transmitted to the... 

All the RyR channels are gated by cytoplasmic Ca2+, known as Ca2+-induced Ca2+ release (CICR). CICR functions as an amplifier of small Ca2+ signals in various excitable and non-excitable tissues and well documented in E-C coupling in the heart. In addition, RyRl can also mediate depolarization-induced Ca2+ release (DICR) , which is controlled by some protein-protein interactions. DICR is the principal Ca2+ release mode in E-C coupling in the skeletal muscle. 

C. Increasing Gliosome [Ca2+] by Membrane Depolarization Induces Glutamate Release... 

Phthalide 30 dose-dependently relaxed phenylephrine- and KCl-induced precontractions in aortas isolated from spontaneous hypertensive rats [354]. Neither endothelium removal nor /V°-nitro-L-arginine methyl ester (L-NAME) affected the vasodilatory response of 30 [354], These results were not in line with Xu s observation that 30 stimulated NO release from bovine aortic endothelial cells [342]. Phthalide 30 also non-competitively right-shifted cumulative phenylephrine and high K+-depolarized Ca2+ dose-response curves but did not affect caffeine-induced Ca2+ release from internal stores [354]. The discrepancies among experiments may have been due to the differences in the choice of animals and preparations utilized. 

Calcium couples muscle membrane excitation to filament contraction. Important work has focused on the proteins present in the T-tubule/SR junction. One protein, an integral component of the T-tubular membrane, is a form of L-type, dihydropyridine-sensitive, voltage-dependent calcium channel. Another, the ryanodine receptor (RyR), is a large protein associated with the SR membrane in the triad that may couple the conformational changes in the Ca2+ channel protein induced by T-tubular depolarization to the Ca2+ release from the SR (Fig. 43-6). 

In muscle cells, the contraction is induced by Ca2+ release from the sarcoplasmic reticulum, as a result of membrane depolarization and activation of RyRl receptors located at the surface of the SR. The subsequent transport of cytoplasmic Ca2+ back into the lumen of the sarcoplasmic reticulum restores low resting calcium levels and allows muscle relaxation. In fast-twitch skeletal muscle fibers, Ca2+ uptake is mediated by the sarco(endo)plasmic reticulum Ca2+ ATPase SERCA1 which represents more than 99% of SERCA isoforms in these muscle fibers. 

Presynaptic G-protein coupled receptors for a large number of neurotransmitters, both autoreceptors and receptors for extrinsic signals, suppress Ca2+-channel gating in response to an action potential. This mechanism of action appears to be the dominant mechanism involved in short-term plasticity mediated by presynaptic receptors. A typical example is depolarization-induced suppression of inhibition (DSI), which is the short-term suppression of presynaptic GABA-release induced by the depolarization of the postsynaptic cell (Diana and Marty, 2004). DSI is caused when the postsynaptic depolarization causes the release of endocannabinoids from the postsynaptic cell, and the endocannabinoids then bind to presynaptic CB1 receptors whose activation suppresses presynaptic Ca2+-channels. Like many other forms of presynaptic suppression mediated by activation of presynaptic receptors, this effect is short-lasting (in the millisecond range). The precise mechanisms by which Ca2+-channels are suppressed appear to vary between receptors, but the outcome is always a very effective short-term decrease in synaptic signaling. 

The ability of a-LTX to trigger neurotransmitter exocytosis in the absence of extracellular Ca2+ remains particularly interesting and inexplicable to the field (Longenecker et al. 1970 Ceccarelli et al. 1979 see also Siidhof (2001) and Ushkaryov et al. (2004) for review). This is clearly different from depolarization-induced exocytosis, which is Ca2+-dependent, but not unlike the effect of hypertonic sucrose. The possibility that a-LTX-induced release involves an unknown, Ca2+-independent mechanism which may also occur during normal synaptic activity has provided the casus belli for many a quest for a-LTX structure and receptors that could trigger neurotransmission via intracellular mechanisms. 

Presynaptic H3 receptors also are uniform in their signal transduction. They couple to Gi/o proteins and decrease the depolarization-induced release of neurotransmitters by inhibiting multiple calcium channels (e.g., Arrang et al. 1985 Schlicker et al. 1994 Endou et al. 1994 Brown and Haas 1999 see Stark et al. 2004). For comparison, the signal transduction of soma-dendritic H3 autoreceptors in histamin-ergic neurons also involves a pertussis toxin-sensitive G-protein with subsequent inhibition of N- and P-type Ca2+ channels (Takeshita et al. 1998). The few exceptions to this signal transduction pathway are discussed in the corresponding subsections below (see Sections 3.1, 3.3, and 3.9). 

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